1. Field of the Invention
This invention concerns novel derivatives of certain bicyclo[4.2.0]octanes and pharmaceutically acceptable salts and esters thereof, their use in treating cardiovascular disorders, pharmaceutical compositions containing these compounds, and methods of preparing such compounds.
2. Related Disclosures
Bicyclo[4.2.0]oct-2-en-7-one is readily prepared from 1,3-cyclohexadiene (Tetrahedron, 27:615, 1971). This has been used as an intermediate in a prostaglandin synthesis (Tetrahedron Lett., 3091, 1973).
Several prostaglandin analogues are known which contain bicyclic all-carbon skeletons. Carbacyclin contains a bicyclo[3.3.0]octane skeleton, and is described in several publications (J. Chem. Soc., Chem. Commun., 1067, 1978, Tetrahedron Lett., 3743, 1978; Tetrahedron Lett., 433, 1979; Tetrahedron Lett., 2807, 1979; J. Org. Chem. 44:2880, 1979) and patents (Belgium Pat. No. 874, 135; British Pat. No. 2,014,143; French Pat. No. 2,424,908; Ger. Offen. 2,904,655; Japanese Pat. No. K79,117,450; Netherthland Patent Application Nos. 7,901,076 and 8,003,579; S. African Pat. No. 79 00 176). Numerous analogues of carbaprostacyclin are described (U.S. Pat. No. 4,306,076; Ger. Offen. No. 3,146,278; Ger. Offen. No. 3,204,443; Prostaglandins, Leukotrienes Med., 9:307, 1982; J. Org. Chem. 48, 5341, 1983; Tetrahedron Lett. 3493, 1983; Biochem. Pharmacol. 32:2405, 1983; Prostaglandins, Leukotrienes. Med. 11:391, 1983). 9-Substituted analogs of carbacyclin are described in U.S. Pat. No. 4,487,960 and U.S. Pat. No. 4,487,961.
Synthetic prostaglandins (homo PGE.sub.2 and homo PGF.sub.2.alpha.) have been prepared with the hydroxyl function and lower side chain trans-opposed in a 6-membered ring (Tetrahedron Lett., 3327, 1971).
The preparation of novel unsubstituted bicyclo[4.2.0]octane derivatives and their use in treating cardiovascular disorders was disclosed in U.S. patent application Ser. No. 716,872, filed 03/27/85, the relevant portions of which are incorporated by reference herein.